DESCRIPTION (Applicant's abstract): The overall goal of this proposal is to determine the role of the bronchial circulation in the uptake of soluble, hydrophilic particles from the surface of conducting airways. The bronchial artery perfuses the airways from the level of the carina to respiratory bronchioles. Uptake into the mucosal capillaries of the bronchial vasculature provides systemic access of all soluble particles that are deposited on the airway surface and traverse the epithelium. Thus, both therapeutically and toxicologically active particles can be taken up by the bronchial vasculature. Using inert, radiolabeled, hydrophilic particles (technetium-99m-labeled diethylenetriamine pentaacetic acid) and gamma camera counting and imaging, the time course of soluble particle clearance from the airway surface and uptake by the bronchial microvasculature will be determined in sheep in which the bronchial artery is cannulated and bronchial blood flow controlled. How changes in blood flow affect the uptake of labeled particles deposited specifically in the conducting airways will be determined. Furthermore, the importance of bronchial perfusion on particle uptake after eliciting changes in the airway wall that are a consequence of bronchial vascular pathology will be studied. These include airway wall edema, induced by the infusion of bradykinin directly into the bronchial artery and bronchial vascular engorgement resulting from left atrial hypertension. Using fluorescent microspheres infused directly into the bronchial artery, we will determine whether changes in perfusion distribution account for the mechanism by which alterations in uptake occur. These studies will provide new information regarding the extent of soluble particle uptake by the systemic circulation of the conducting airways. Furthermore, the results will contribute to an understanding of the factors that both limit and enhance uptake and distribution of aerosols.